An HLA-linked human gene, Bevi (mapped to 6p21-6pter) regulates baboon endogenous retrovirun infection in human x rodent somatic cell hybrids. A critical feature of Bevi gene action is that hybrid cells infected with baboon endogenous virun (BEV) shows all evidence of retroviral expression (antigens and virus production) following segregation of hum,an chromosome 6. The molecular cloning and chromosomal assignment of BEV proviruses in hybrid cells shows that Bevi is not a preferred integration domain but, rather, acts in trans to regulate retroviral integration or expression at other sites in the human genone. The specific aims of this proposal are to use molecular biological techniques (1) to investigate the precise genetic function of the Bevi gene; 92) to elucidate viral and cellular target sequences recognized by the Bevi coded protein; and (3) to determine the biochemical properties of the Bevi gene product. These studies will take advantage of a unique bank of genetically characterized somatic cell hybrid clones that differentially express the Bevi gene. DNA constructs derived from a biologically active, molecularly cloned BEV provirus will be used to elucidate Bevi gene function. Since the human genome does not contain BEV DNA, the normal target of Bevi gene action cannot be BEV itself. An attractive hypothesis is that the Bevi gene product regulates other transcriptional units that bear homology to BEV sequences. The use of retroviral DNA constructs to study Bevi function permits assays for an HLA-linked gene product that may hierarchically control the expression of other human genes.